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Trends Biochem Sci. 2012 Apr;37(4):134-43. doi: 10.1016/j.tibs.2012.01.002. Epub 2012 Feb 28.

Inositol 5-phosphatases: insights from the Lowe syndrome protein OCRL.

Author information

1
Department of Cell Biology, HHMI and Program in Cellular Neuroscience, Neurodegeneration and Repair, Yale University School of Medicine, New Haven, CT 06510, USA.

Abstract

The precise regulation of phosphoinositide lipids in cellular membranes is crucial for cellular survival and function. Inositol 5-phosphatases have been implicated in a variety of disorders, including various cancers, obesity, type 2 diabetes, neurodegenerative diseases and rare genetic conditions. Despite the obvious impact on human health, relatively little structural and biochemical information is available for this family. Here, we review recent structural and mechanistic work on the 5-phosphatases with a focus on OCRL, whose loss of function results in oculocerebrorenal syndrome of Lowe and Dent 2 disease. Studies of OCRL emphasize how the actions of 5-phosphatases rely on both intrinsic and extrinsic membrane recognition properties for full catalytic function. Additionally, structural analysis of missense mutations in the catalytic domain of OCRL provides insight into the phenotypic heterogeneity observed in Lowe syndrome and Dent disease.

PMID:
22381590
PMCID:
PMC3323734
DOI:
10.1016/j.tibs.2012.01.002
[Indexed for MEDLINE]
Free PMC Article

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